J Pediatr Res 2018;5(2):100-2 DO I: 10.4274/jpr.32154 Case Report Triple X Syndrome with a Rare Finding: Cleft Palate Esra Gürkaş1, Hülya Maraş Genç1, Esra Kılıç 2 1 University of Health Sciences, Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital, Clinic of Pediatric Neurology, Ankara, Turkey 2 University of Health Sciences, Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital, Clinic of Pediatric Genetics, Ankara, Turkey ABS TRACT Triple X syndrome (trisomy X) is a sex chromosomal anomaly caused by the presence of an extra X chromosome. The patients with Triple X syndrome have a wide range of phenotypic variability. Some individuals are only mildly affected or asymptomatic. Epicanthal folds, clinodactyly, tall stature and hypotonia are the most commom phenotypic features. Patients also may have seizures, genitourinary abnormalities and premature ovarian failure. We report a patient with Triple X syndrome and cleft palate. By describing this case, we want to draw attention to the association between cleft palate and Triple X syndrome. Keywords: Triple X, trisomy X, cleft palate, seizure Introduction Case Report Triple X syndrome (47,XXX) is a sex chromosomal A 11-year old girl was admitted to our neurology clinic abnormality. Affected females have an extra X chromosome. with seizure. She was the second child of healthy unrelated This syndrome was described by Jacobs et al. (1). Incidence parents. The age of mother at conception was 31 years old. is approximately 1/10.000 females (2). There is a wide There was no problem during the antenatal period and phenotypic variability of patients with triple X. Phenotypic ultrasound scans were reported as normal. CP was identified findings include epicanthal folds, clinodactyly, tall stature and in the first examination after delivery. She required 1 week hypotonia. Also, clinical findings are seizures, genitourinary of neonatal care for feeding difficulties. She was operated on for CP. She was able to sit without support at 8 months abnormalities, premature ovarian failure, intentional tremor, and walk without support at 14 months of age. She had congenital hip dysplasia, constipation/abdominal pains delayed milestones in speech-language development. She (2,3). However, most of the woman with Triple X syndrome pronounced her first words at the age of 3 years after speech presents indistinct clinical signs. Herein, we report on a therapy. She was able to produce her first sentences at 4 patient with Triple X syndrome and cleft palate (CP). Cleft lip years of age. She also had mild learning disabilities and a and palate were described only in one paper describing two poor academic performance. Wechsler Intelligence scale patients with Triple X syndrome. There is only one paper in for Children-Revised was used for the assessment of her the literature describing cleft lip and palate in two patients cognitive skills. Her verbal, performance and full-scale scores with Triple X syndrome (4). In the light of these findings, were 57, 79 and 66 respectively. There was no family history of co-occurrence of cleft lip and palate and Triple X syndrome either epilepsy or neurodevelopmental disorders. On physical should be considered. examination, she was 133 cm (3 percentile) with a weight of Ad dress for Cor res pon den ce Esra Gürkaş MD, University of Health Sciences, Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital, Clinic of Pediatric Neurology, Ankara, Turkey Phone: +90 533 250 04 55 E-mail: [email protected] ORCID ID: orcid.org/0000-0003-3942-5105 Re cei ved: 23.11.2016 Ac cep ted: 08.02.2017 ©Copyright 2018 by Ege University Faculty of Medicine, Department of Pediatrics and Ege Children’s Foundation The Journal of Pediatric Research, published by Galenos Publishing House. 100 Gürkaş et al. Triple X Syndrome with a Rare Finding: Cleft Palate 27 kg (3-10 percentile) and a head circumference of 54.6 cm department as her findings included CP, learning disabilities (50-98 percentile). She had a long face with an open mouth and seizure. Chromosome analysis using G-band technique appearance (Figure 1, 2). She had received dental treatment. revealed a 47,XXX karyotype (Figure 3). The fluorescent She did not have hypertelorism, epicanthal folds, clinodactyly, in situ hybridization analysis (FISH) of 22q11.2 locus was overlapping digits, pes planus or pectus excavatum. normal signal pattern with no deletion. After the diagnosis The patient had generalized tonic-clonic seizure of Triple X syndrome, in order to investigate the abnormalities with a prolonged post-ictal period. Wake and sleep associated with this syndrome, an abdominal ultrasound and echocardiography were performed and both of them were electroencephalogram showed normal background activity normal. Genetic counselling was provided to the patient and and no epileptic discharge. Brain magnetic resonance imaging her family. Her family was informed about the recurrence was normal. Sodium valproate treatment was started and rate, which is estimated to be below 1%. her epilepsy was well controlled. She was referred to a genetic Figure 3. 47,XXX karyotype of the patient Discussion Triple X syndrome is the most common female chromosomal abnormality. Due to a nondisjunction event in the cell division, during gametogenesis or after conception, Figure 1. Patient with long face with open mouth appearance X chromosomes fail to properly separate resulting in a numerical abnormality. Triple X has a significant correlation with advanced maternal age (2). Most patients with Triple X syndrome are asymptomatic or mildly affected so approximately only 10% of patients are diagnosed (2). Minor physical findings including hypertelorism, epicanthal folds, up-slanting palpebral fissures, clinodactyly, overriding digits, pectus excavatum and pes planus can be seen (2,3). Genitourinary malformations including renal dysplasia, unilateral kidney, ovarian malformations, premature ovarian failure, primary amenorrhea and congenital heart defects such as atrial and ventricular septal defects, pulmonic stenosis and aortic coarctation have also been described (2). Seizure disorders can be seen in 15% of patients. Different seizure types including absence, partial and generalized tonic clonic seizures have been described but complex partial seizures are the most commonly seen type. A good response to standard anticonvulsant treatment has been described. The most preferred antiepileptic drugs are carbamazepine, sodium valproate and clobazam (2,5). Our patient also Figure 2. Patient with operated cleft palate presented with generalized seizures and seizure control 101 Gürkaş et al. Triple X Syndrome with a Rare Finding: Cleft Palate was achieved with sodium valproate treatment. Patients urinary tract infections and mullerian abnormalities. Brain with Triple X syndrome also have developmental and computed tomography revealed parietal bone agenesis. She psychological problems in variable degrees. Early milestone had developmental delay and had been receiving speech delays in motor and speech-language development can be therapy. There were differences between our case and that seen. Speech and language deficits can continue during the reported by Jagadeesh et al. (4), these two patients have school and adolescent period (3). There is a wide variation multiple phenotypic and clinical findings, but our patient in full-scale intelligence quotients of children with triple X has indistinct clinical signs. The only similarity between our ranging from 55-115 (2). Our patient also had mild learning patient and the reported second case was a delay in speech difficulties. In cleft lip and CP, the upper lip and roof of the development. Our case provides a rare example of Triple mouth are affected. When CP is associated with two or X syndrome with CP. We cannot conclude that there is a more malformations, then it is called syndromic CP. If it is causal relationship between these two but we want to draw isolated or cannot be associated with a recognizable pattern, attention to the possible association between triple X and CP. it is called non-syndromic CP. Environmental and genetic Ethics factors may be responsible for cleft lip and palate. Several Informed Consent: Was obtained from the patient and genes causing syndromic CP have been discovered. The his parent. T-box transcription factor-22 gene, located on chromosome Peer-review: External and Internal peer-reviewed. Xq21, is important in the etiology of syndromic cleft lip and palate (6). Maternal smoking, maternal alcohol use, Authorship Contributions folate deficiency and anticonvulsant (phenytoin/hydantoin, Surgical and Medical Practices: E.G., H.M.G., E.K., Design: valproic acid and topiramate) treatment during pregnancy E.G., H.M.G., E.K., Data Collection and Processing: E.G., are environmental factors associated with orofacial clefts. H.M.G., E.K., Analysis and Interpretation: E.G., H.M.G., E.K., Palatal anomalies were found in approximately 70% of Literature Search: E.G., H.M.G., E.K., Writing: E.G., H.M.G., E.K. patients with 22q11.2 Deletion syndrome so the FISH of Conflict of Interest: No conflict of interest was declared 22q11.2 locus was performed for our patient, a normal signal by the authors. pattern with no deletion was detected. According to the Lyon Financial Disclosure: The authors declared that this hypothesis, one of the X chromosome in females is randomly study has received no financial support. selected and inactivated early in the embryonic development so each female has only one active X chromosome. But References in the majority of human triploid cells, more than one X 1. Jacobs P, Baikie AG, Brown WM, Macgregor TN, Maclean chromosome is active (7). Fryns et al. (8) and Ramaekers et N, Harnden DG. Evidence for the existence of the human al. (9) suggested that the over expression of genes located “superfemale”. Lancet 1959;2:423-5. on the X chromosome may have a gene dosage effect and 2. Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L.